Neanderthal DNA Shapes Clinical Traits for Modern Humans

Modern humans have inherited many physical traits from the Neanderthals. John Capra, Ph.D., from Vanderbilt University, explains how many of these variants affect a variety of clinical disorders.

This graphic shows some of the numerous Neanderthal-influenced traits. [Deborah Brewington, Vanderbilt University]

Today being the 207th birthday celebration of renowned naturalist and evolutionary biologist Charles Darwin, it seemed only appropriate to discuss the recent findings of how Neanderthal DNA has shaped and continues to shape human evolution.

Recent studies have identified that individuals of Eurasian origins inherited somewhere between one and four percent of their DNA from Neanderthals. These findings have led to numerous postulations about how these genetic variants may have affected physical characteristics or the behavior of modern humans, ranging from skin color to heightened allergies to fat metabolism.

Now, a new study from a team of scientists led by researchers at Vanderbilt University has directly compared Neanderthal DNA in the genomes of a large population of adults from European ancestry with their clinical records—confirming that this archaic genetic legacy has a subtle but significant effect on modern human biology.          

“Our main finding is that Neanderthal DNA does influence clinical traits in modern humans: We discovered associations between Neanderthal DNA and a wide range of traits, including immunological, dermatological, neurological, psychiatric, and reproductive diseases,” explained senior study author John Capra, Ph.D., assistant professor in the department of biomedical informatics and an investigator in the Center for Human Genetics Research at Vanderbilt University Medical School.

The results of this study were published February 12 in Science through an article entitled “The phenotypic legacy of admixture between modern humans and Neanderthals.”

Interestingly, Dr. Capra and his colleagues were able to confirm a few of the previous hypotheses about the influence of Neanderthal DNA on modern Homo sapiens. For instance, the investigators found that Neanderthal DNA affects keratinocytes, which help protect the skin from environmental damage such as ultraviolet radiation and pathogens. The new analysis found Neanderthal DNA variants influence skin biology in modern humans, in particular, the risk of developing sun-induced skin lesions called keratosis, which are caused by abnormal keratinocytes. 

Surprisingly, the research team found that some regions of Neanderthal DNA were associated with psychiatric and neurological effects. In one example, they found that a specific bit of Neanderthal DNA significantly increased the risk for nicotine addiction, while a separate set of variants influenced the risk for depression (positively and negatively). 

“The brain is incredibly complex, so it's reasonable to expect that introducing changes from a different evolutionary path might have negative consequences,” noted lead author and Vanderbilt doctoral student Corinne Simonti.

In the current study, the authors discussed that the pattern of associations they discovered suggests today's population retains Neanderthal DNA that may have provided modern humans with some adaptive advantages 40,000 years ago as they migrated into regions outside of Africa with different pathogens and levels of sun exposure.

To study these associations, the scientists used a database containing 28,000 patients whose biological samples have been linked to anonymized versions of their electronic health records. The data came from eMERGE—the Electronic Medical Records and Genomics Network—which links digitized records from Vanderbilt University Medical Center's BioVU databank and eight other hospitals around the country.

This massive amount of genomic data allowed the researchers to determine if each individual had ever been treated for a particular set of medical conditions, such as heart disease, arthritis, or depression. Subsequently, they analyzed the genomes of each individual to identify the unique set of Neanderthal DNA that each person carried. The comparison of each data set allowed the researchers to test whether each bit of Neanderthal DNA individually and in aggregate influences risk for the traits derived from the medical records.

“Vanderbilt's BioVU and the network of similar databanks from hospitals across the country were built to enable discoveries about the genetic basis of disease,” Dr. Capra remarked. “We realized that we could use them to answer important questions about human evolution.”

While Dr. Capra and his colleagues were thrilled by their findings—this work establishes a new way to investigate questions about the effects of events in recent human evolution—the researcher team also realized that there is a lot of additional information contained in the medical records, such as lab tests, doctors' notes, and medical images, that could be used in future analyses to refine their data.